Repeatability of Quantitative Autofluorescence Imaging in a Multicenter Study Involving Patients With Recessive Stargardt Disease 1

Translational Vision Science & Technology, vol. 12, pp. 1

Abstract

Purpose: This study assesses the repeatability of quantitative autofluorescence (qAF) in a multicenter setting and evaluates qAF as the end point for clinical trials in recessive Stargardt disease 1 (STGD1). Methods: A total of 102 patients with STGD1 underwent qAF imaging as part of the Stargardt Remofuscin Treatment Trial (STARTT; EudraCT No. 2018-001496-20). For 166 eyes, we obtained qAF imaging at 2 visits, with 2 recordings per visit. The qAF8 values were independently determined by the study site and a central reading center. Intra- and inter-visit reproducibility, as well as interobserver (study site versus reading center) reproducibility were obtained using intraclass correlation (ICC), one-sample t-test, and Bland-Altman coefficient of repeatability. Results: The qAF repeatability was ± 26.1% for intra-visit, ± 40.5% for inter-visit, and ± 20.2% for the interobserver reproducibility measures. Intra-visit repeatability was good to excellent for all sites (ICC of 0.88-0.96). Variability between visits was higher with an overall ICC of 0.76 (0.69-0.81). We observed no significant difference in qAF values across sites between visits (7.06 ± 93.33, P = 0.238). Conclusions: Real-life test-retest variability of qAF is higher in this set of data than previously reported in single center settings. With improved operator training and by selecting the better of two recordings for evaluation, qAF serves as a useful method for assessing changes in autofluorescence signal. Translational Relevance: The qAF can be adopted as a clinical trial end point, but steps to counterbalance variability should be considered.

Authors 14

1. Patty P.A. Dhooge

   Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands

   Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands

2. Philipp T. Möller

   University of Bonn

   Affiliation as printed

   Department of Ophthalmology, University of Bonn, Bonn, Germany

   GRADE Reading Center, Bonn, Germany

3. Nils Meland

   Smerud Medical Research (Norway)

   Affiliation as printed

   SMERUD Medical Research International AS, Thunes vei 2, Oslo, Norway

4. Katarína Štingl

   University of Tübingen

   Affiliation as printed

   Univeristy Eye Hospital, Center for Ophthalmology, University of Tuebingen, Tuebingen, Germany

5. Camiel J. F. Boon Aachen Department of Ophthalmology, Leiden University Medical Center

   Leiden University Medical Center · Amsterdam University Medical Centers

   Affiliation as printed

   Department of Ophthalmology, Amsterdam University Medical Centers, Amsterdam, The Netherlands

   Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands

6. Andrew John Lotery

   University of Southampton

   Affiliation as printed

   Faculty of Medicine, University of Southampton, Southampton, UK

7. Maurízio Battaglia Parodi

   IRCCS Ospedale San Raffaele

   Affiliation as printed

   Department of Ophthalmology, Ospedale San Raffaele, Milano, Italy

8. Philipp Herrmann

   University of Bonn

   Affiliation as printed

   Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany

   Department of Ophthalmology, University of Bonn, Bonn, Germany

9. Wolfgang Klein
   Affiliation as printed

   Katairo GmbH, Kusterdingen, Germany

10. Mario G. Fsadni

    Pharma Foods International Co., Ltd. (Japan)

    Affiliation as printed

    International Pharm-Med Ltd., Bramhall, UK

    Katairo GmbH, Kusterdingen, Germany

11. Thomas H. Wheeler‐Schilling

    University of Tübingen

    Affiliation as printed

    Center for Ophthalmology and Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany

12. Frank Gerhard Holz

    University of Bonn

    Affiliation as printed

    Department of Ophthalmology, University of Bonn, Bonn, Germany

    GRADE Reading Center, Bonn, Germany

13. Carel B. Hoyng corresponding

    Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

    Affiliation as printed

    Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands

    Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands

14. Steffen Schmitz-Valckenberg

    University of Bonn · University of Utah

    Affiliation as printed

    Department of Ophthalmology, University of Bonn, Bonn, Germany

    GRADE Reading Center, Bonn, Germany

    John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA